Flow synthesis of quantum dot nanocrystals

ABSTRACT

Nanocrystals are synthesized with a high degree of control and hence product quality control in a flow-through reactor in which the reaction conditions are maintained by on-line detection of characteristic properties of the product and by adjusting the reaction conditions accordingly. The coating of nanocrystals is achieved in an analogous manner.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention resides in the field of nanocrystalline materialsand processes for their manufacture.

[0003] 2. Description of the Prior Art

[0004] Quantum-sized particles, i.e., those having diameters within therange of about 0.1 nm to about 50 nm, also known as quantum dots ornanocrystals, are known for the unique properties that they possess as aresult of both their small size and their high surface area. Some ofthese particles have unique magnetic properties that make the particlesuseful in electronic data systems such as recording media, in ferrofluids, and in magnetic tagging elements. Luminescent nanocrystals areparticularly useful as detectable labels such as oligonucleotides tags,tissue imaging stains, protein expression probes, and the like, inapplications such as the detection of biological compounds both in vitroand in vivo. Luminescent nanocrystals offer several advantages overconventional fluorophores, particularly for multiplexed and/or highsensitivity labeling. Nanocrystals typically have larger absorptioncross sections than comparable organic dyes, higher quantum yields,better chemical and photochemical stability, narrower and more symmetricemission spectra, and a larger Stokes shift. Furthermore, the absorptionand emission properties vary with the particle size and can besystematically tailored.

[0005] A variety of methods have been reported for the preparation ofnanocrystals. These methods include inverse micelle preparations,arrested precipitation, aerosol processes, and sol-gel processes. Amethod commonly used for the preparation of binary nanocrystals is onein which an organometallic and elemental set of nanocrystal precursorsis injected into a hot solvent as the solvent is being stirred. Productnucleation can begin immediately, but the injection causes a drop in thesolvent temperature, which tends to halt the nucleation process.Nucleation and particle growth can be continued by heating the reactionmixture with further stirring, and the temperature can be dropped tostop the reaction when the desired particle size is obtained. As aresult, the success of this batchwise “stirred-pot” method is stronglyaffected by system parameters such as the initial temperature of thesolvent, the injection temperature and in particular the injection rate,the stirring efficiency, the concentrations of the reactant materials,the length of time that the mixture is held at the reaction temperature,and the efficiency of the cooling both after injection and after thedesired endpoint is achieved. Some of these parameters are difficult tocontrol with precision, and this can lead to poor reproducibility of theproduct. The lack of precise control also leads to nanocrystals withsurfaces that are nonuniform, products that are readily degradable,and/or nanocrystals with low emission quantum yields.

[0006] The initial reaction conditions, i.e., the manner and conditionsunder which the reaction is initiated, are particularly important incontrolling the quality and uniformity of the product, and far more sothan in other types of syntheses. Stirred-pot methods suffer in thisregard since there are limits to how rapidly and uniformly thetemperature of the reaction mixture can be changed or otherwisecontrolled. The temperature drop that occurs upon injection of theprecursors will vary with the precursor temperature prior to injection,the volume of precursor injected and its rate of injection, the volumeof the heated solvent, and the stirring efficiency. The difficulty incooling rapidly when terminating the reaction often means that a lowerreaction temperature must be used as a means of avoiding excessreaction. Further difficulties with stirred-pot methods are that theyoften involve the injection of large volumes of flammable or pyrophoricmaterials at very high temperatures, or the rapid evolution of gases,all of which present safety hazards.

[0007] Control of the properties of nanocrystals by the application ofcoatings or shells has been reported, notably in International PatentPublication No. WO 99/26299 (PCT/US98/23984), “Highly LuminescentColor-Selective Materials,” Massachusetts Institute of Technology,applicant, international publication date May 27, 1999, and referencescited therein. The application of an inorganic shell, for example, canincrease the quantum yield of the nanocrystal as well its chemicalstability and photostability. The techniques for applying a shell arestirred-pot techniques that are usually similar to those used for thepreparation of the core. Like the diameter of the core, the thickness ofthe shell affects the properties of the finished product, and thethickness will vary with the same system parameters that affect thecore. The difficulties in controlling these parameters in a stirred-potsystem lead to difficulties in controlling the nature and quality of thefinal product.

SUMMARY OF THE INVENTION

[0008] The limitations and difficulties described above and othersencountered in the preparation of nanocrystals are addressed by thepresent invention, which resides in processes and apparatus for theproduction of monodisperse luminescent semiconductor nanocrystals, forthe application of a coating to nanocrystal cores, and for both. Themanufacture of nanocrystals in accordance with this invention isaccomplished by first dissolving or dispersing precursor materialscapable of reacting to form nanocrystals in a solvent, for example acoordinating solvent, and introducing the resulting reaction mixtureinto a reaction tube that is embedded or immersed in a heat transfermedium. Likewise, the application of a coating to nanocrystal cores inaccordance with this invention is accomplished by dispersing thenanocrystal cores in a solvent, for example a coordinating solvent, inwhich are dissolved the precursor materials for the coating, andintroducing this reaction mixture into the reaction tube. In eithercase, the heat transfer medium is maintained at the desired reactiontemperature, and the reaction mixture is passed continuously through thetube. The internal diameter of the tube is preferably small enough topromote rapid transfer of heat from the tube walls to the center of thefluid stream flowing through the tube and hence rapid heating of thecontinuously flowing stream to the reaction temperature. In addition tothe tube diameter, the flow rate is varied and adjusted, and the tubelength selected, to permit control of the reaction. Flow rate,temperature and pressure are all controllable, and in preferredembodiments the reaction is quenched by cooling the product stream uponits emergence from the reaction tube by any of various conventionalcooling techniques.

[0009] Characteristic properties of the product stream, such as opticalproperties, electrical properties, magnetic properties, electromagneticproperties, and the like are detected and a comparison is made betweenthe detected values and a predetermined or preselected target range thatis indicative of the product quality sought to be achieved. Anydiscrepancy or deviation between the detected values and target rangecan then be used to adjust the variable reaction conditions, such as thetemperature of the heat transfer medium, the flow rate of the reactionmixture through the tube, or both, until the product changessufficiently that the detected values fall within or otherwise conformto the target range.

[0010] Reaction apparatus in accordance with this invention includes athermally conductive reaction tube of sufficiently small internaldiameter to accomplish effective heat transfer in the flowing stream, aheat transfer medium in thermal contact with the exterior of thereaction tube, a pump or other fluid-driving component for continuouslysupplying a reactant or precursor mixture to the reaction tube, amonitoring unit to evaluate, measure, or otherwise detect the propertiesof the product stream, preferably but not necessarily as the productstream leaves the reaction tube, as an indication of the nature andquality of the nanocrystals formed in the reaction mixture during itspassage through the reaction tube, and optionally a control loop toadjust the reaction conditions in the tube to correct for anydiscrepances between the detected values and the target range.

[0011] Further details of these features and the various preferredembodiments of the several aspects of this invention are describedbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 is a process flow diagram of one embodiment of the presentinvention.

[0013]FIG. 2 is a process flow diagram of a second embodiment of thepresent invention.

[0014]FIG. 3 is a superimposed plot of emission spectra of nanocrystalsformed by the process and apparatus of the present invention undervarious reaction conditions.

DETAILED DESCRIPTION OF THE INVENTION AND SPECIFIC EMBODIMENTS

[0015] The terms “semiconductor nanocrystal,” “quantum dot,” “Qdot™nanocrystal,” or simply “nanocrystal” are used interchangeably hereinand refer to an inorganic crystallite between about 1 nm and about 1000nm in diameter or any integer or fraction therebetween, more typicallyabout 2 nm to about 20 nm (such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, or 20 nm). A semiconductor nanocrystal iscapable of emitting electromagnetic radiation upon excitation (i.e., thesemiconductor nanocrystal is luminescent) and includes a “core” of oneor more first semiconductor materials, and may be surrounded by a“shell” of a second semiconductor material. A semiconductor nanocrystalcore surrounded by a semiconductor shell is referred to as a“core/shell” semiconductor nanocrystal. The surrounding “shell” materialtypically has a bandgap energy that is larger than the bandgap energy ofthe core material and can be chosen to have an atomic spacing close tothat of the “core” substrate. The core and/or shell can be asemiconductor material including, but not limited to, those of theGroups II-VI (ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS,MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, and thelike) and III-V (GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, and thelike) and IV (Ge, Si, and the like), and alloys or mixtures thereof.

[0016] By “luminescence” is meant the process of emittingelectromagnetic radiation (light) from an object. Luminescence resultsfrom a system that is “relaxing” from an excited state to a lower statewith a corresponding release of energy in the form of a photon. Thesestates can be electronic, vibronic, rotational, or any combination ofthese three. The transition responsible for luminescence can bestimulated through the release of energy stored in the system chemicallyor added to the system from an external source. The external source ofenergy can be of a variety of types including chemical, thermal,electrical, magnetic, electromagnetic, physical, or any other typeexcited by absorbing a photon of light, by being placed in an electricfield, or through a chemical oxidation-reduction reaction. The energy ofthe photons emitted during luminescence can be in a range of low-energymicrowave radiation to high-energy x-ray radiation. Typically,luminescence refers to photons in the range from UV to IR radiation.

[0017] “Monodisperse particles” include a population of particleswherein at least about 60% of the particles in the population, morepreferably 75% to 90% of the particles in the population, or any integerwithin this range, fall within a specified particle size range. Apopulation of monodisperse particles deviates less than 10% rms(root-mean-square) in diameter and typically less than 5% rms. Inaddition, upon exposure to a primary light source, a monodispersepopulation of semiconductor nanocrystals is capable of emitting energyin narrow spectral linewidths, as narrow as 12 nm to 60 nm full width ofemissions at half peak height (FWHM), and with a symmetric, nearlyGaussian line shape. As one of ordinary skill in the art with recognize,the linewidths are dependent on, among other things, the sizeheterogeneity, i.e., monodispersity, of the semiconductor nanocrystalsin each preparation. Certain single semiconductor nanocrystal complexeshave been observed to have FWHM as narrow as 12 nm to 15 nm.

[0018] One of the implementations of this invention is the formation ofnanocrystalline particles (or nanocrystal cores for encapsulation). Thisis done in a continuous-flow manner, and precursors known in the art maybe used. Useful precursors are many and varied, depending on the type ofnanocrystals to be prepared and the intended use of the nanocrystals.One of the various classes of nanocrystals are those that emit light,and examples are those bearing the empirical formulae CdX or ZnX inwhich X is a chalcogen. Preferred chalcogens are S, Se and Te, with Separticularly preferred. Preferred nanocrystals are CdSe, CdS, CdTe, andZnSe. Reactants capable of forming nanocrystals of these materials areorganocadmium and organozinc compounds as the source of the Cd and Zn,respectively, and elemental chalcogen or chalcogen-containing compoundsas the source of the chalcogen.

[0019] Other implementations of the invention are the coating ofpre-formed nanocrystal cores. The coating is likewise performed in acontinuous-flow manner, by placing the cores in a suspension in whichstarting material(s) that form the coating are dissolved. Coatings ofvarious compositions known in the art can be applied in this manner. Oneclass of coatings are those serving to passivate the cores to improveoptical properties such as quantum yield. Among this class are thosebearing the empirical formula ZnY in which Y is S, Se, or a mixturethereof.

[0020] Whether the reaction is a nanocrystal core-forming reaction or acoating reaction, the process is often facilitated by performing thereaction in the presence of a coordinating solvent or by addition of acoordinating additive. The terms “coordinating solvent” and“coordinating additive” as used herein denote a solvent or otherchemical additive that enters into molecular coordination with the atomsin the reactants that combine to form the nanocrystalline materials orthe reactants that combine to form the coatings on the nanocrystal coresurfaces or with the nanocrystals themselves. The coordinating solventthus enhances the solubility of the reactants while also serving as ameans of modulating the reactivity of the precursors or the growingnanoparticles. A wide range of solvents that function in this manner canbe used, and a preferred group are alkyl phosphines, alkyl phosphineoxides, pyridines, furans, ethers, amines and alcohols. Coordinatingsolvents that are particularly preferred for cadmium chalcogenidenanocrystals are tri-n-octylphosphine and tri-n-octylphosphine oxide. Acoordinating solvent that is particularly preferred for zincchalcogenide nanocrystals is hexadecylamine. In certain embodiments ofthe invention, notably Cd-Se systems, a mixture of tri-n-octylphosphineand tri-n-octylphosphine oxide offers particular benefits, the formerpotentially serving as a preferential coordinator for Se and the latterfor Cd.

[0021] The reactions performed in accordance with this invention areperformed on a continuous-flow basis in the thermally conductivereaction tube. The tube is thermally conductive in order to permitefficient heat transfer between the heat transfer medium surrounding thetube and the reaction mixture flowing through the tube. As will be wellappreciated by those skilled in the art, the efficiency of the heattransfer is also dependent on the internal diameter and wall thicknessof the tube and the composition of the heat transfer medium surroundingthe tube. While this invention is not intended to be limited to specificvalues for the diameter and length of the tube, the optimal values ofthese dimensions will be determined by considerations of the viscosityof the reaction mixture and the pressure drop needed to drive thereaction mixture through the tube, both of which will depend on theconcentration of the reactants in the reaction mixture as well as thetemperature. These types of determinations can be made by routineexperimentation, or by the use of relationships that are well knownamong those skilled in fluid dynamics. In general, however, successfulresults will be obtained with a reaction tube having an internaldiameter of about 1.0 mm or less, and preferably within the range ofabout 0.1 mm to about 1.0 mm, and most preferably within the range offrom about 0.25 mm to about 0.8 mm. The reaction tube will have a wallthickness be great enough to provide dimensional stability andsturdiness to the tube but the wall will otherwise be as thin aspossible. If the tube material itself has a high heat conductivity, thenthe tube will contribute to the heat transfer and the choice of wallthickness will be of little importance. In some cases, as describedbelow, the reaction tube may be continuous with the surrounding heattransfer medium, with essentially no wall thickness.

[0022] The temperature changes imposed on the reaction mixture duringits passage through the reaction tube will likewise depend on the tubediameter, as well as the flow rate of the reaction mixture. Flow ratesmay vary, and the invention is not intended to be limited to specificflow rates. Nevertheless, effective results will be achieved at flowrates within the range of from about 10 μL per minute to about 1000 μLper minute, preferably from about 30 μL per minute to about 300 μL perminute.

[0023] The degree or extent of reaction also depends on theconcentrations of the reactants, the length of the reaction tube, andthe temperature and pressure at which the reaction tube is maintained.None of these operating parameters are limited to specific values inthis invention, and each may vary considerably in accordance with thetype of product being prepared and the characteristics and qualitiesthat are sought in the product. The appropriate selection of theseparameters is a matter of routine skill to those experienced or familiarwith batchwise processes for these reactions. In most applications, itis contemplated that the reaction tube will be from about 3 cm to about300 cm in length, preferably from about 10 cm to about 100 cm in length.Likewise, the most typical temperatures will be at least about 100° C.,and preferably within the range of from about 100° C. to about 400° C.,more preferably within the range of about 250° C. to about 400° C. Thesetemperature ranges are applicable to both the nanocrystal core-formingreaction and the coating reaction.

[0024] The reaction tube itself may be of any configuration that willpermit continuous flow and that can be immersed, embedded or otherwiseplaced in full thermal contact with a heat transfer medium. The tube canbe straight, serpentine, coiled, or otherwise shaped. The tube can bemade of a variety of materials based upon requirements such as thermalconductivity, flexibility, or chemical reactivity. The tube can also beof composite construction, such as glass-coated stainless steel, toobtain particular combinations of properties. The heat transfer mediumcan be gas, liquid, or solid. With gas or liquid media, circulation canimprove the heat transfer efficiency by creating a more uniformtemperature. A solid heat transfer medium can be formed by casting ormolding a heat conductive material around the reaction tube. If desired,the reaction tube can be formed by forming a bore through a solid blockof heat transfer medium, the bore itself serving as the tube. Aparticularly effective arrangement is the use of a reaction tube with ablock of heat conductive metal cast around the tube. Materials ofconstruction are selected as those that are chemically inert to thereaction materials while providing effective heat transfer.

[0025] Monitoring of the product stream is performed by conventionalapparatus for the on-line detection of the determinative orcharacteristic properties of the product stream. Examples of theseproperties are absorbance of electromagnetic radiation, emission ofelectromagnetic radiation, both absorbance and emission ofelectromagnetic radiation, static or dynamic light scattering,refractive index, conductance, and magnetic susceptibility. Static lightscattering, dynamic light scattering, or refractive index, for example,can be used to assess the size distribution of the particles.Conductance can be used with charged particles to obtain a particlecount, and magnetic susceptibility can be used with magnetic orparamagnetic particles to determine the size distribution, particlecount, or both. All of these properties can be detected by techniquesthat are known in the art using instrumentation that is commerciallyavailable. In the preferred practice of the invention, the propertiesdetected are optical properties such as, for example, emissionintensity, emission wavelength, full width at half maximum peak height,absorption, light scattering, fluorescence lifetime, or combinations ofthese properties. Detection can be performed at a site downstream of thereaction tube and heat transfer medium. Alternatively, detection can beperformed on-line within the reaction tube itself, in which case a tubethat permits such detection is used. For detection of opticalproperties, for example, suitable tubes are those that are opticallytransparent. In preferred implementations of this invention, the productmixture is cooled at or near the site where detection is performed.Thus, when on-line detection is performed, the product mixture ispreferably cooled as it emerges from the heat transfer medium but beforeit reaches the on-line detection point. Cooling in these embodiments isdone to lower the temperature of the product stream enough tosubstantially quench any reaction still occurring in the moving streamand to standardize the detection temperature, thereby eliminatingvariations in the optical properties due to temperature. Cooling can beaccomplished by passing the product stream through a cooling tubeembedded or immersed in a cooling medium in a manner analogous to theheat transfer medium used to heat the starting materials to reactiontemperature. It is often sufficient to cool the material passively bysimply removing the heating element at the end of the reaction zone.Alternatively, cooling can be achieved by diluting the product streamwith additional solvent at an appropriately low temperature. In certainembodiments the injection of additional solvent provides an additionalbenefit—i.e., when the solvent in which the reaction takes place is amixture of species such as tri-n-octylphosphine and tri-n-octylphosphineoxide, one of which has a melting point above room temperature, theaddition of a further amount of a lower-melting solvent species forcooling purposes can prevent freezing of the higher-melting species andfacilitate handling of the product stream.

[0026] The properties that are monitored may be any detectableproperties that serve as an indication of the size of the nanocrystals,the thickness of the coating, the surface characteristics, or in generalthe degree or quality of reaction having occurred in the reaction tube.Absorbance is readily measured by irradiating the product stream withlight and determining the absorption spectra. Light scattering isreadily measured by illuminating the product stream and detecting thedirection or amount of scattered light, either one being characteristicof the properties of the nanocrystals and their chemical composition.Photoluminescence is readily measured by irradiating the product streamwith light of an appropriate wavelength to excite the nanoparticles anddetecting the emission spectra resulting from the excitation.Conventional spectrophotometers or other light detecting devices can beused.

[0027] Comparison of the spectra with a target range is then performedto determine whether adjustments are needed to the reaction conditionsto shift the spectra into the target range. If the shift can be achievedby a change in the reaction temperature, the comparison can serve as ameans of determining how much and in which direction to modify thetemperature of the heat transfer medium and hence the temperature in thereaction tube. The comparison can be performed visually in a trial runor at the start of the process or at any time during the progress of thereaction, and adjustments to the temperature can be made manually by theoperator. Alternatively, the comparison can be performed by automatedinstrumentation, and if desired, on a continuous basis, with acorresponding adjustment in temperature or flow rate until thecomparison produces a favorable result.

[0028] The Figures attached hereto illustrate various embodiments of theinvention in the form of process flow diagrams.

[0029]FIG. 1 is a process flow diagram illustrating one example of arudimentary system embodying the principles of this invention. The firststage is a reagent preparation stage 11 in which nanocrystal precursors(for those embodiments involving the formation of nanocrystal cores) aredissolved in a coordinating solvent, or in which preformed nanocrystalcores (for those embodiments involving the coating of the preformedcores) are suspended in a solution of coating precursors dissolved in acoordinating solvent. In either case, the resulting reaction mixture istransferred by a computer-controlled syringe pump 12 to the heatedreactor 13, which consists of a stainless steel tube 14 whose innerdiameter is 0.01 inch to 0.03 inch (0.25 mm to 0.76 mm) around which azinc block 15 has been cast. The zinc block is provided with temperaturedetection and heating connections that permit temperature control of theblock 15 (and hence the tube 14) to various temperatures up to about400° C. At the outlet of the heated reactor 13, the product streampasses through a flow-through monitoring cell 16 which includes anultraviolet light source to excite the nanocrystals in the productstream and a CCD-based miniature spectrometer to measure the emissionspectra from the nanocrystals. The emission spectra can be monitoredvisually by the operator and adjustments made to the temperature of theheated reactor 13, the syringe pump 12, or both, to achieve nanocrystalsthat emit the desired spectra. Alternatively, the emission spectradetected by the monitor can be transmitted to an automated controller 17which will process the data, compare it to a target spectrum, andtransmit signals to either the heated reactor, the syringe pump, orboth, to correct the temperature and/or flow conditions. This can bedone on a continuous basis until the detected spectra conform to thetarget spectra to a degree that is acceptable to the operator. Thefinished nanocrystals are collected in a product recovery unit 18 whenthe parameters have been adjusted sufficiently to achieve the desiredspectral output.

[0030] An optional added feature in FIG. 1 is the provision of theintroduction of cooled diluent 19 to the product stream emerging fromthe reactor 13 for purposes of quenching the reaction prior to theproduct mixture reaching the monitoring cell. The diluent 19 is fedthrough a metering pump 20 to an on-line mixing chamber 21 where itmixes with the product stream.

[0031] In variations of the system illustrated in FIG. 1, two or morereagents can be supplied by individual pumping units, each underseparate control from a centralized controller. As in FIG. 1, thecontroller signals to the pumping units can be modulated by comparisonsof the spectral output of the product stream, thereby adjusting therelative feed rates of the reagents to achieve a product having thedesired spectral characteristics. Likewise, monitoring cells can beplaced at two or more locations along the process flow path to monitorthe progress of the reaction. This will allow different reagents to beadded at different stages of the process, and is particularly usefulwhen the process is used both to form the nanocrystal core and to coatthe core. The outputs of all monitoring cells will be received andprocessed either by individual controllers or by a common controller,and resulting signals emitted by the controller(s) can be used to driveadjustments in the temperatures or pump rates at various points alongthe process path. For reactions performed in two or more stages,separately controlled heating units can be used so that each stage canbe individually controlled to its own optimum temperature. For systemsthat include monitoring cells at two or more locations, individualcooling sites can be incorporated immediately upstream of the entry toeach cell. In certain systems, it may also be desirable to extract,concentrate, or isolate product from the product stream at pointsbetween successive stages of the process. Operations such as these canbe performed by centrifugation, precipitation, filtration, and othersimilar treatments that are well known to those with experience inprocess chemistry.

[0032]FIG. 2 is a process flow diagram for a process that includes firstpreparing the nanocrystal core and then applying a coating to the core,incorporating several of the additional features of the precedingparagraph. The core is formed in a heated reactor 41 which is similar inconstruction to that of FIG. 1, supplied by two reagents 42, 43, eachfed by individual metering pumps 44, 45, then preheated 46, 47, andcombined in a mixing chamber 48 prior to entry into the reactor 41. Thepreheating is optional and may be used when the resulting mixture mightsuffer a drop in temperature due to the addition of one of thecomponents, or when one of the solvents is a solid at room temperature.The two metering pumps 44, 45 drive the reaction mixture through thereactor 41, and the emerging dispersion of nanocrystal cores is cooledby the introduction of a cooled diluent 49, likewise supplied through ametering pump 50 and mixed with the core dispersion in a mixing chamber51. The cooled product stream passes through a monitoring cell 52 whichdetects the optical properties of the nanocrystal cores in the productstream and forwards the data to a controller 53 where the data iscompared to a target and corrective output signals are transmitted tothe two reagent metering pumps 44, 45, and to the heating unit on theheated reactor 41.

[0033] The core suspension, upon emerging from the monitor 52, iscombined with coating agent(s) to prepare for the coating reactionwhich, like the nanocrystal-forming reaction, occurs at an elevatedtemperature. The coating agent(s) 54 are supplied through a meteringpump 55 and mixed with the core dispersion in a mixing chamber 56. Theflow diagram presents two options for delivering the core suspension tothe mixing chamber—direct delivery and delivery through a processingunit 57 where the core suspension is concentrated or otherwise treatedas described above to prepare the cores for coating. In either case, thenew reaction mixture enters the second heated reactor 61, which issimilar in construction and principle to the first heated reactor 41.The product stream emerging from the second heated reactor contains thecoated nanocrystals, and is cooled by a diluent 62 fed through ametering pump 63 and mixed with the product stream in a mixing chamber64. The cooled coated nanocrystal stream then enters a second monitoringcell 65 which detects the optical properties of the coated cores andforwards the data to a second controller 66 where the data is comparedto a target and corrective output signals are transmitted to the coatingagent metering pump 53 and the heating unit on the heated reactor 61.The product stream is then processed in a processing unit 67 where thecoated nanocrystals are recovered from the solvent and any unreactedmaterial.

[0034] The following example is offered as illustration, and is notintended to impose limits on the scope of the invention.

EXAMPLE

[0035] This example demonstrates the use of the present invention inpreparing nanocrystals of CdSe, and the ability of an on-linefluorescence monitoring cell to differentiate between products preparedat different reaction temperatures, flow rates and the like.

[0036] A solution was prepared by dissolving 0.179 g of selenium in 16mL of tri-n-octylphosphine (TOP) and adding 0.115 mL of dimethylcadmium. Separately, tri-n-octylphosphine oxide (TOPO) (12.5 g) washeated under vacuum to 180° C. and then maintained at 65° C. under drynitrogen. The heated TOPO was then combined with 7 mL of the TOPsolution of selenium and dimethyl cadmium. A continuous-flow reactionwas then performed, using the apparatus depicted in FIG. 1, with areaction tube consisting of 50 cm of 0.03-inch (0.76 mm) stainless steeltubing coiled tightly and cast into a zinc block. The flow rate of thereaction mixture through the tubing was 200 μL/minute, and the zincblock was variously maintained at temperatures of 280° C., 290° C., 300°C., 310° C., 320° C., 330° C., 340° C., 350° C., and 365° C.

[0037] Luminescence spectra were obtained for the emerging productformed at each of the nine reaction temperatures, and the results areshown in superimposed curves in FIG. 3. The superimposed curves showthat each reaction temperature produced a distinct curve, and thatadjustment of the reaction temperature can therefore be used to obtain aproduct of a particular emission spectrum while still maintaining anarrow size distribution of the particles, as indicated by the peakwidths.

[0038] The foregoing description is offered for illustrative purposes.Those skilled in the art will recognize that further modifications,variations and substitutions in the process and apparatus parameters,such as temperatures, flow rates, reactant materials and othercomponents of the reaction and product mixtures, as well as the numberand arrangement of operating units in the process flow path, can be madewithout departing from the spirit and scope of the invention.

What is claimed is:
 1. A process for the preparation of monodisperseluminescent semiconductor nanocrystals having detectable propertieswithin a target range, said method comprising: (a) combiningnanocrystal-forming reactants with a solvent to form a solution; (b)continuously passing said solution at a selected flow rate through athermally conductive reaction tube embedded in a heat transfer mediummaintained at a temperature sufficiently high to initiate a reactionamong said reactants, thereby producing a product mixture containingnanocrystals; (c) monitoring said product mixture to detect propertiesof said nanocrystals that are indicative of the degree to which saidnanocrystals possess desired characteristics; and (d) comparing thevalue of said properties thus detected with said target range andadjusting either the temperature of said heat transfer medium, the flowrate of said solution, or both, if needed to correct any deviationbetween said value of said detected properties and said target range. 2.A process in accordance with claim 1 in which said properties thusdetected are optical properties.
 3. A process in accordance with claim 1further comprising cooling said product mixture between steps (b) and(c) to a temperature sufficiently low to quench said reaction.
 4. Aprocess in accordance with claim 1 in which step (c) is performed uponemergence of said product mixture from said reaction tube.
 5. A processin accordance with claim 3 in which said cooling is performed bycombining additional solvent with said product mixture, said additionalsolvent being at a temperature and a proportion relative to said productmixture sufficient to achieve a final temperature sufficiently low toquench said reaction.
 6. A process in accordance with claim 2 in whichsaid optical features are photoluminescent emission spectra, and step(c) comprises irradiating said product mixture with light and detectingwavelength spectra of photoluminescent energy emitted from saidnanocrystals.
 7. A process in accordance with claim 2 in which saidoptical features are absorbance, and step (c) comprises irradiating saidproduct mixture with light and detecting absorbance spectra of saidnanocrystals.
 8. A process in accordance with claim 2 in which saidoptical features are light scattering, and step (c) comprisesirradiating said product mixture with light and detecting the presenceof light scattering by said nanocrystals.
 9. A process in accordancewith claim 1 in which said thermally conductive reaction tube is acoiled tube cast in a solid block of heat conductive metal.
 10. Aprocess in accordance with claim 1 in which said heat transfer medium ofstep (b) is maintained at a temperature of at least about 100° C.
 11. Aprocess in accordance with claim 1 in which said heat transfer medium ofstep (b) is maintained at a temperature of from about 100° C. to about400° C.
 12. A process in accordance with claim 1 in which saidnanocrystal-forming reactants are (i) a member selected from the groupconsisting of an organocadmium compound and an organozinc compound and(ii) a member selected from the group consisting of an elementalchalcogen and a chalcogen-containing compound.
 13. A process inaccordance with claim 12 in which said chalcogen is a member selectedfrom the group consisting of sulfur, selenium, and tellurium.
 14. Aprocess in accordance with claim 12 in which said chalcogen is selenium.15. A process in accordance with claim 1 in which said nanocrystalcomprises a member selected from the group consisting of CdSe, CdS,CdTe, and ZnSe.
 16. A process in accordance with claim 1 in which saidcoordinating solvent is a member selected from the group consisting ofalkyl phosphines, alkyl phosphine oxides, pyridines, furans, ethers,amines, and alcohols.
 17. A process in accordance with claim 1 in whichsaid solvent is a member selected from the group consisting oftri-n-octylphosphine and tri-n-octylphosphine oxide.
 18. A process inaccordance with claim 1 in which said solvent is a mixture oftri-n-octylphosphine and tri-n-octylphosphine oxide.
 19. A process inaccordance with claim 1 in which step (d) comprises adjusting thetemperature of said heat transfer medium.
 20. A process in accordancewith claim 1 in which step (d) comprises adjusting the flow rate of saidsolution.
 21. A process for the coating of nanocrystals with apassivating coating to achieve coated nanocrystals having detectableproperties within a target range, said method comprising: (a) combiningnanocrystal cores with surface passivating reactants and a coordinatingsolvent to form a dispersion; (b) continuously passing said dispersionthrough a thermally conductive reaction tube embedded in a heat transfermedium maintained at a temperature sufficiently high to initiate areaction among said passivating reactants, thereby producing a productmixture containing nanocrystals coated with a passivating coating; (c)monitoring said product mixture to detect properties of saidnanocrystals that are indicative of the degree to which saidnanocrystals possess desired characteristics; and (d) comparing valuesof said properties thus detected with said target range and adjustingthe temperature of said heat transfer medium, the flow rate of saidsolution, or both, if needed to correct any deviation between saidvalues of said detected properties and said target range.
 22. A processin accordance with claim 21 in which said surface passivating reactantsare a Zn-containing reactant and a reactant containing a member selectedfrom the group consisting of S and Se, and said passivating coating is acoating of ZnY in which Y is a member selected from the group consistingof S, Se, and mixtures of S and Se.
 23. A process in accordance withclaim 21 in which step (c) is performed upon emergence of said productmixture from said reaction tube.
 24. A process in accordance with claim22 in which said surface passivating reactants are a dialkyl zinc andhexamethyldisilathiane.
 25. A process in accordance with claim 21further comprising cooling said product mixture between steps (b) and(c) to a temperature sufficiently low to quench said reaction.
 26. Aprocess in accordance with claim 21 in which said properties are opticalfeatures.
 27. A process in accordance with claim 26 in which saidoptical features are photoluminescent emission spectra, and step (c)comprises irradiating said product mixture with light and detectingwavelength spectra of photoluminescent energy emitted from saidnanocrystals.
 28. A process in accordance with claim 26 in which saidoptical features are absorbance, and step (c) comprises irradiating saidproduct mixture with light and detecting absorbance spectra of saidnanocrystals.
 29. A process in accordance with claim 26 in which saidoptical features are light scattering, and step (c) comprisesirradiating said product mixture with light and detecting the presenceof light scattering by said nanocrystals.
 30. A process in accordancewith claim 21 in which said heat transfer medium of step (b) ismaintained at a temperature of from about 100° C. to about 400° C.
 31. Aprocess in accordance with claim 21 in which said coordinating solventis a member selected from the group consisting of alkyl phosphines,alkyl phosphine oxides, pyridines, furans, ethers, amines, and alcohols.32. A process in accordance with claim 21 in which said coordinatingsolvent is a member selected from the group consisting oftri-n-octylphosphine and tri-n-octylphosphine oxide.
 33. A process inaccordance with claim 21 in which said coordinating solvent is a mixtureof tri-n-octylphosphine and tri-n-octylphosphine oxide.
 34. A process inaccordance with claim 21 in which step (d) comprises adjusting thetemperature of said heat transfer medium.
 35. A process in accordancewith claim 21 in which step (d) comprises adjusting the flow rate ofsaid solution.
 36. Apparatus for the fabrication of monodisperseluminescent semiconductor nanocrystals having detectable propertieswithin a target range, said apparatus comprising: a thermally conductivereaction tube embedded in a heat transfer medium; heating means formaintaining said heat transfer medium at a temperature sufficiently highto initiate a nanocrystal-forming reaction between nanocrystal-formingreactants passing therethrough; pump means for continuously passing afluid carrier bearing nanocrystal-forming reactants through saidthermally conductive reaction tube at a reaction flow rate; monitormeans for monitoring a product stream borne by said fluid carrier todetect properties of any nanocrystals formed therein that are indicativeof the degree to which said nanocrystals possess desiredcharacteristics; and control means for comparing values of said opticalfeatures thus detected with said target range and adjusting thetemperature of said heat transfer medium, the pump rate of said pumpmeans, or both, if needed to correct any deviation between said valuesof said detected optical features and said target range.
 37. Apparatusin accordance with claim 36 in which said properties are opticalfeatures.
 38. Apparatus in accordance with claim 37 in which saidoptical features are photoluminescent emission spectra, and said monitormeans comprise means for irradiating said product mixture with light anddetecting wavelength spectra of photoluminescent energy emitted fromsaid nanocrystals.
 39. Apparatus in accordance with claim 37 in whichsaid optical features are absorbance, and said monitor means comprisemeans for irradiating said product mixture with light and detectingabsorbance spectra of said nanocrystals.
 40. Apparatus in accordancewith claim 37 in which said optical features are light scattering, andsaid monitor means comprise means for irradiating said product mixturewith light and detecting the presence of light scattering by saidnanocrystals.
 41. Apparatus in accordance with claim 36 furthercomprising cooling means for cooling said product mixture borne by saidfluid carrier upstream of said monitor means.
 42. Apparatus inaccordance with claim 36 in which said monitor means monitors saidproduct stream as it emerges from said thermally conductive reactiontube.
 43. Apparatus in accordance with claim 36 in which said controlmeans adjusts the temperature of said heat transfer medium. 44.Apparatus in accordance with claim 36 in which said control meansadjusts the pump rate of said pump means.